Annals of Surgical Oncology

, Volume 21, Issue 8, pp 2782–2800 | Cite as

Systematic Review and Meta-Analysis Comparing the Surgical Outcomes of Invasive Intraductal Papillary Mucinous Neoplasms and Conventional Pancreatic Ductal Adenocarcinoma

  • Ye-Xin Koh
  • Aik-Yong Chok
  • Hui-Li Zheng
  • Chuen-Seng Tan
  • Brian K. P. Goh
Pancreatic Tumors



The aim of this study was to summarize the current literature comparing the surgical outcomes of invasive intraductal papillary mucinous neoplasms (IPMNINV) and conventional pancreatic ductal adenocarcinomas (PDAC) in order to determine the differences in disease characteristics and prognosis.


Systematic review of the literature yielded 12 comparative studies reporting the clinicopathological characteristics and overall survival (OS) of 1,450 patients with IPMNINV with 19,304 patients with conventional PDAC.


IPMNINV had a significantly lower likelihood of tumors extending beyond the pancreas [27.6 vs. 94.3 %; T4 vs. T1: odds ratio (OR) 0.111, 95 % confidence intervals (CI) 0.057–0.214], nodal metastasis (45.4 vs. 62.9 %: OR 0.507, 95 % CI 0.347–0.741), positive margin (14.2 vs. 28.3 %; OR 0.438, 95 % CI 0.322–0.596), perineural invasion (49.2 vs. 76.5 %; OR 0.304, 95 % CI 0.106–0.877) and vascular invasion (25.2 vs. 45.7 % OR 0.417, 95 % CI 0.177–0.980) when compared with PDAC. The 5-year OS of IPMNINV was significantly better than PDAC [31.4 vs. 12.4 %: hazard ratio (HR) 0.659, 95 % CI 0.574–0.756]. The tubular subtype had a poorer 5-year OS and demonstrated significantly more aggressive features such as nodal metastases, vascular invasion, and perineural invasion compared with the colloid subtype.


IPMNINV were significantly more likely to present at an earlier stage and were less likely to demonstrate nodal involvement, perineural invasion and vascular invasion. When controlled for stage, IPMNINV had an improved OS when compared with PDAC in the early stages.


Overall Survival Vascular Invasion Intraductal Papillary Mucinous Neoplasm Perineural Invasion Tubular Adenocarcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Kloppel G, Solcia E, Longnecker DS, Capella C, Sobin LH. Histological typing of exocrine pancreas. Berlin. Springer; 1996.CrossRefGoogle Scholar
  2. 2.
    Goh BK, Tan YM, Cheow PC, et al. Cystic neoplasms of the pancreas with mucin-production. Eur J Surg Oncol. 2005;31:282–287.PubMedCrossRefGoogle Scholar
  3. 3.
    Goh BK, Tan YM, Chung YF, et al. A review of mucinous cystic neoplasms of the pancreas defined by ovarian-type stroma: clinicopathologic features of 344 patients. World J Surg. 2006;30(12):2236–45.PubMedCrossRefGoogle Scholar
  4. 4.
    Longnecker DS, Adler G, Hruban RH, Kloppel G. Intraductal papillary-mucinous neoplasms of the pancreas. In: Hamilton SR, Bltonen LA, editors. Pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000:237e40.Google Scholar
  5. 5.
    Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: anupdated experience. Ann Surg. 2004;239(6):788–97.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Wada K, Kozarek RA, Traverso LW. Outcomes following resection of invasive and noninvasiveintraductal papillary mucinous neoplasms of the pancreas. Am J Surg. 2005;189(5):632–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Sohn TA, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Lillemoe KD. Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg. 2001;234(3):313–21.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Schnelldorfer T, Sarr MG, Nagorney DM, et al. Experience with 208 resections for intraductal papillary mucinous neoplasm of the pancreas. Arch Surg. 2008;143(7):639–46.PubMedCrossRefGoogle Scholar
  9. 9.
    Nara S, Shimada K, Sakamoto Y, Esaki M, Kosuge T, Hiraoka N. Clinical significance of frozen section analysis during resection of intraductal papillary mucinous neoplasm: should a positive pancreatic margin for adenoma or borderline lesion be resected additionally? J Am Coll Surg. 2009;209:614–621.PubMedCrossRefGoogle Scholar
  10. 10.
    Crippa S, Fernández-del Castillo C, Salvia R, et al. Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiologic characteristics. Clin Gastroenterol Hepatol. 2010;8:213–219.Google Scholar
  11. 11.
    Salvia R, Fernandez-del Castillo C, Bassi C, et al. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg. 2004;239(5):678–85.Google Scholar
  12. 12.
    Maire F, Hammel P, Terris B, et al. Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma. Gut. 2002;51(5):717–22.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Wasif N, Bentrem DJ, Farrell JJ, Ko CY, Hines OJ, Reber HA, et al. Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes. Cancer. 2010;116(14):3369–77.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Yamaguchi K, Kanemitsu S, Hatori T, et al. Pancreatic ductal adenocarcinoma derived from IPMN and pancreatic ductal adenocarcinoma concomitant with IPMN. Pancreas. 2011;40(4):571–80.PubMedCrossRefGoogle Scholar
  15. 15.
    Waters JA, Schnelldorfer T, Aguilar-Saavedra JR, et al. Survival after resection for invasive intraductal papillary mucinous neoplasm and for pancreatic adenocarcinoma: a multi-institutional comparison according to American Joint Committee on Cancer Stage. J Am Coll Surg. 2011;213(2):275–83.PubMedCrossRefGoogle Scholar
  16. 16.
    Yopp AC, Katabi N, Janakos M, et al. Invasive carcinoma arising in intraductal papillary mucinous neoplasms of the pancreas: a matched control study with conventional pancreatic ductal adenocarcinoma. Ann Surg. 2011;253(5):968–74.PubMedCrossRefGoogle Scholar
  17. 17.
    Poultsides GA, Reddy S, Cameron JL, et al. Histopathologic basis for the favorable survival after resection of intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma of the pancreas. Ann Surg. 2010;251(3):470–6.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Japan Pancreas Society. Classification of pancreatic carcinoma. 2nd English ed. Tokyo: Kanehara & Co, Ltd; 2003.Google Scholar
  20. 20.
    Sobin LH, Wittekind C; International Union Against Cancer. TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss; 2002.Google Scholar
  21. 21.
    Fleming ID, Cooper JS, Henson D, et al. AJCC cancer staging manual. 5th ed. New York: Lippincott-Raven; 1997.Google Scholar
  22. 22.
    Schlesselman J, Stolley P. Case-control studies, design, conduct, analysis. New York: Oxford University Press; 1982.Google Scholar
  23. 23.
    Shimada K, Sakamoto Y, Sano T, Kosuge T, Hiraoka N. Invasive carcinoma originating in an intraductal papillary mucinous neoplasm of the pancreas: a clinicopathologic comparison with a common type of invasive ductal carcinoma. Pancreas. 2006;32(3):281–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Woo SM, Ryu JK, Lee SH, Yoo JW, Park JK, Kim YT, et al. Survival and prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas: comparison with pancreatic ductal adenocarcinoma. Pancreas. 2008;36(1):50–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakashima A, et al. Invasive intraductal papillary-mucinous neoplasm of the pancreas: comparison with pancreatic ductal adenocarcinoma. J Surg Oncol. 2009;100(1):13–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Mino-Kenudson M, Fernández-del Castillo C, Baba Y, et al. Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes. Gut 2011;60(12):1712–20.Google Scholar
  27. 27.
    Chinn S. A simple method for converting an odds ratio to effect size for use in meta-analysis. Stat Med 2000;19:3127–3131.PubMedCrossRefGoogle Scholar
  28. 28.
    Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidermiol Rev. 1992;14:154–176.Google Scholar
  30. 30.
    Kang MJ, Lee KB, Jang JY, Kwon W, Park JW, Chang YR, et al. Disease spectrum of intraductal papillary mucinous neoplasm with an associated invasive carcinoma invasive IPMN versus pancreatic ductal adenocarcinoma-associated IPMN. Pancreas. 2013;42(8):1267–74.PubMedCrossRefGoogle Scholar
  31. 31.
    Sadakari Y, Ohuchida K, Nakata K, et al. Invasive carcinoma derived from the nonintestinal type intraductal papillary mucinous neoplasm of the pancreas has a poorer prognosis than that derived from the intestinal type. Surgery. 2010;147(6):812–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Goh BK, Tan YM, Cheow PC, Chung YF, Chow PK, Wong WK, et al. Outcome of distal pancreatectomy for pancreatic adenocarcinoma. Dig Surg. 2008;25(1):32–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Le H, Ziogas A, Rhee JM, Lee JG, Lipkin SM, Zell JA. A population-based, descriptive analysis of malignant intraductal papillary mucinous neoplasms of the pancreas. Cancer Epidemiol Biomarkers Prev. 2008;17(10):2737–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Goh BK, Thng CH, Tan DM, et al. Evaluation of the Sendai and 2012 International Consensus Guidelines based on initial cross-sectional imaging findings for the management of mucinous cystic lesions of the pancreas: a single institution experience with 114 surgically-treated patients. Am J Surg. Epub 17 Jan 2014.Google Scholar
  35. 35.
    Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10(9):1199–210.PubMedCrossRefGoogle Scholar
  36. 36.
    Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223(3):273–279.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Konstantinidis IT, Vinuela EF, Tang LH, et al. Incidentally discovered pancreatic intraepithelial neoplasia: what is its clinical significance? Ann Surg Oncol. 2013;20:3643–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Goh BK, Tan DM, Thng CH, et al. Are the Sendai and Fukuoka consensus guidelines for mucinous neoplasms of the pancreas useful in the initial triage of all suspected pancreatic cystic neoplasms? A single institution experience with 317 surgically-treated patients. Ann Surg Oncol. Epub 7 Feb 2014.Google Scholar
  39. 39.
    Goh BK, Tan DM, Ho MF, Lim KH, Chung AY, Ooi LL. Utility of the Sendai consensus guidelines for branch-duct intraductal papillary mucinous neoplasms: a systematic review. J Gastrointestin Surg. In press.Google Scholar
  40. 40.
    Fritz S, Fernandez-del Castillo C, Mino-Kenudson M, et al. Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma. Ann Surg. 2009;249(3):440–7.Google Scholar
  41. 41.
    Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6:17–32.Google Scholar
  42. 42.
    Salvia R, Partelli S, Crippa S, et al. Intraductal papillary mucinous neoplasms of the pancreas with multifocal involvement of branch ducts. Am J Surg. 2009;198(5):709–14.PubMedCrossRefGoogle Scholar
  43. 43.
    Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297(3):267–77.PubMedCrossRefGoogle Scholar
  44. 44.
    Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473–1481.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Ye-Xin Koh
    • 1
  • Aik-Yong Chok
    • 1
  • Hui-Li Zheng
    • 2
  • Chuen-Seng Tan
    • 2
  • Brian K. P. Goh
    • 1
    • 3
  1. 1.Department of Hepatopancreatobiliary and Transplant Surgery, Division of SurgerySingapore General HospitalSingaporeSingapore
  2. 2.Saw Swee Hock School of Public HealthNational University of SingaporeSingaporeSingapore
  3. 3.Office of Clinical SciencesDuke-NUS Graduate Medical SchoolSingaporeSingapore

Personalised recommendations